Vitamin D supplementation for the prevention of pre-eclampsia? ‘First do no harm’


Authors’ Reply


We thank Kaptanis et al.1 for their interest in our study on longitudinal vitamin D status in relation to the risk of pre-eclampsia.2 We agree with their comments, which underline the importance of gaining more information before recommending routine supplementation of vitamin D in pregnant women.

First, Kaptanis et al. discussed the potential role of vitamin D in the prediction of the pre-eclampsia. Our main finding is an association between maternal lower vitamin D levels and the risk of pre-eclampsia, suggesting that vitamin D deficiency may be a modifiable risk factor for pre-eclampsia. ‘Association’ is not equal to ‘prediction’. At present, there is no evidence to recommend the measurement of maternal vitamin D levels as part of a screening programme for pre-eclampsia.

Second, only one relatively small trial3 involving 400 pregnant women evaluated the role of vitamin D (1200 IU/day) and calcium supplementation in the prevention of pre-eclampsia. The intervention did not produce an isolated effect of the vitamin D supplementation on the incidence of pre-eclampsia. This study was underpowered to demonstrate anything other than a very large effect.

In a recent trial,4 women with a singleton pregnancy (n = 502) at 12–16 weeks of gestation were allocated to 400, 2000 or 4000 IU/day vitamin D3 until delivery. The relative risk for achieving a concentration of 80 nmol/l or greater within 1 month of delivery was significantly different between the 4000-IU and the 400-IU groups (relative risk 1.60, 95% CI 1.32–1.95). However, this trial did not report the effect of the treatments on the pregnancy outcomes.

Clearly, the dose of vitamin D that is required in pregnant women to achieve target pregnancy outcomes in a manner that is safe for both the mother and the fetus remains to be determined. As well, there is a need for a better understanding of the potential mechanisms of action of vitamin D, if any, on the pathophysiology of pre-eclampsia. Furthermore, carefully conducted phase II trials will maximise the likelihood of success of subsequent phase III trials in this area.